Hemostatic complications of cardiac surgery often occur for reasons that are not well understood. Despite efforts to limit blood loss and blood product transfusion, cardiac surgery patients consume 10-20% of the nation?s blood supply. Postoperative thrombotic events, such as coronary graft occlusion, are often unpredictable, and cause appreciable morbidity, resource utilization, such as need for additional revascularization. Many risk factors for these complications have been identified; among these, it is known that activation of the coagulation system occurs during cardiopulmonary bypass (CPB) and is responsible for mediating substantial postoperative hemostatic impairment. Although contact system activation unquestionably occurs during CPB, the role of the extrinsic system has not been characterized. Extrinsic system activation does occur on CPB, and may be the major contributor to thrombin generation. Furthermore, genetic variants within the genes for tissue factor, factor VII, and tissue factor pathway inhibitor have been described, and many of these significantly influence the activity of their respective protein gene products. However, the impact of these polymorphisms in contributing toward extrinsic system activation during CPB is undescribed. The overall goal of this study is to evaluate the contribution of extrinsic system variation toward observed variability in thrombin generation and impairment of hemostasis following CPB, and identify specific genetic variants in the extrinsic system that may place patients at increased risk for coagulation system abnormalities following CPB. This understanding will assist clinicians in identifying cardiac surgery patients at increased risk for hemostatic abnormalities, and target novel therapies toward those patients most likely to benefit. The project will make extensive use of data in the Vanderbilt Cardiac Surgery Registry, a valuable database of genetic and clinical data presently being prospectively collected on elective adult cardiac surgery patients.